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Ischemia followed by reperfusion (I/R) is an important factor in the progression of cerebral stroke and other types of brain injury. In this study, we examined the effects of repeated cycles of I/R on vascular tone and the expression of the maxi-K(Ca) channel in cerebral arterioles of pigs. For this purpose, we used a model of transient bilateral carotid artery occlusion. Heterogeneous groups of pigs were subjected to either 20 episodes (group 20x) or 40 episodes (group 40x) of 15-min/15-min I/R. In the last protocol, the reperfusion period was followed by 15-min occlusion. The significant prolongation of the reperfusion periods associated with the multiple I/R cycles resulted in significant vasoconstriction to the K(Ca) channel activator Bay K 8644 (10(-7) mol/l) and reduction of maxi-K(Ca) channel expression. Vasoconstriction of cerebral arterioles to nitric oxide and hyperosmolar solutions, along with the alterations observed in the maxi-K(Ca) channel expression, were similar to those induced by a single episode of I/R. These alterations might be mediated by protein kinase C activation during the reperfusion periods. Thus, repeated cycles of I/R are a major factor responsible for induction of vasoconstriction and impairment of the maxi-K(Ca) channel expression in cerebral arterioles. The results of the present study suggest that the maxi-K(Ca) channel may represent a possible molecular target to protect against microvascular dysfunction associated with cerebral ischemia/reperfusion.The Ninjaneers Motorcycling Club meet from 8.30am to 9.15am on 3rd Sunday each month and is held on the North Country Trail. Members are welcome to drop into the clubhouse for refreshments and
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